5. Amino acid degradation and gluconeogenesis

It is often believed that gluconeogenesis from amino acids is
induced during starvation to provide glucose and that the need to provide
glucose is a driving factor in the increased gluconeogenesis taking place after
trauma and during disease (KINNEY and ELWYN, 1983). This view may or may not
include the belief that gluconeogenesis from amino acids is a minor process in
the fed state. In fact, conversion of the glucogenic moieties of the degraded
amino acids to glucose occurs even in the fed state. A detailed quantitative
analysis of the energy exchanges associated with the degradation of amino acids
in man (JUNGAS et al., 1992) demonstrates that gluconeogenesis and export
of glucose is essential, because complete oxidation of the amino acid mixture by
the liver would provide much more ATP than needed by this organ. Gluconeogenesis
from amino acids must thus be regarded as a normal process associated with amino
acid degradation, occurring at higher rates under conditions of normal food
intake than during fasting.

The activation of pyruvate dehydrogenase by insulin is one of the
mechanisms allowing insulin to promote carbohydrate oxidation (DENTON et
al., 1987). The first irreversible steps in the degradation of the
branched-chain amino acids are catalyzed by a-ketoacid oxidizing enzyme
complexes which are similar to PDH and can also be activated by insulin (HARPER
et al., 1984). It seems that glucose availability and the readiness to
oxidize pyruvate which are enhanced by insulin explain the carbohydrate-sparing
effect of exogenous carbohydrate (Figure 3). However, high insulin levels
also open the pathway for the irreversible degradation of the BCAA, notably in
skeletal muscle. Since the BCAA are indispensable amino acids, their loss by the
irreversible oxidation of their a-keto derivatives condems the other amino
acids to being degraded as well, since they cannot be used for protein synthesis
without enough
BCAA.